Long‑term outcomes of prophylactic cranial irradiation in high‑risk metastatic NSCLC: Final PRoT‑BM analysis

To report long-term outcomes of prophylactic cranial irradiation (PCI) versus observation in high-risk advanced non-small-cell lung cancer (NSCLC).

PRoT-BM is an open-label, single-center, phase II randomized trial. Adults with stage IIIB/IV NSCLC at high risk for brain metastases (BM) and no baseline CNS disease were assigned (1:1) to PCI (25 Gy/10 fractions) plus standard therapy or standard therapy alone. The primary endpoint was 24-month cumulative BM incidence; this update evaluates 5-year BM incidence, overall survival (OS), leptomeningeal carcinomatosis, and long-term neurocognitive function (NCF).

Eighty-four patients were randomized (May 2012-December 2017); 81 comprised the efficacy cohort (PCI, n = 38; control, n = 43). At median follow-up of 77.3 months, PCI reduced BM risk by 60% (HR 0.40; 95% CI 0.21-0.78; p = 0.007), with 60-month cumulative incidence of 51.7% versus 78.3%. Median OS was 30.51 versus 19.23 months (HR 0.46; 95% CI 0.28-0.74; p = 0.002); a sensitivity analysis restricted to EGFR-mutant patients (n = 32 per arm) confirmed a consistent benefit (HR 0.57; 95% CI 0.33-0.99; p = 0.045). Leptomeningeal events were infrequent (5-year incidence 11.5% vs 17.4%; HR 0.51; p = 0.29). MMSE-assessed NCF showed no between-arm differences through 24 months; at 48 months, PCI-treated survivors maintained more stable scores than controls (p = 0.006), with no evidence of progressive radiation-related neurotoxicity.

In high-risk metastatic NSCLC, PCI durably reduced BM incidence, prolonged OS, and preserved neurocognitive function over six years of follow-up. These single-center phase II findings warrant multicenter phase III confirmation.